The proposed research project will focus on an examination of mechanisms responsible for the adverse respiratory effects of common environmental and occupational air pollutants. The project will take place at NYU's Institute of Environmental Medicine which is committed to the investigation and understanding of the adverse health effects of pollutants. The primary goal of this research plan is to identify inflammatory cells and mediators involved in the acute and chronic pulmonary injury produced by inhaled agents. The proposed experiments will focus on the contribution of contaminating endotoxin to the airway diseases produced by organic dusts. The candidate will also continue his research interest in the pulmonary effects of ozone and participate in a cooperative, multispecies study examining the pathological changes produced by chronic exposure to ozone alone or in combination with acid, its major co-pollutant. Endotoxin and submicron-size zinc oxide particles share common features with ozone: 1) peripheral lung deposition and injury; 2) development of tolerance- adaptive changes in the lung which appear to protect the respiratory system from repeated exposures; and 3) induction of stress proteins. Experiments will be conducted to determine whether these stress proteins play a role in the well documented development of tolerance in human subjects to the pulmonary and/or systemic effects of ozone, ZnO (metal fume fever) and cotton dust. Thus, the long term career goals of the candidate are: 1) determining the pathways involved in the progression of chronic pulmonary disease produced by inhaled toxicants, and 2) understanding the adaptive mechanisms which occur in the lung to minimize decrements in gas exchange, the primary function of the respiratory system. The award will provide a stable environment and ensure adequate research time to develop cellular and molecular techniques to examine the role of inflammatory cells and mediators in the in vivo effects of inhaled pollutants in animals and apply these techniques to human exposure scenarios.